protein
Voltage-dependent calcium channel subunit alpha-2/delta-3
Gene
CACNA2D3
Organism
Homo sapiens(9606)
Length
1091 aa
Mass
123,011 Da
CACNA2D3 encodes the alpha-2/delta-3 subunit of voltage-dependent calcium channels (UniProt: Q8IZS8). This regulatory subunit modulates calcium current density and the activation/inactivation kinetics of P/Q-type, N-type, and L-type calcium channels, functioning as an auxiliary component that fine-tunes channel behavior without directly forming the ion-conducting pore.
The protein is expressed across tissues requiring calcium-dependent signaling and is particularly relevant in neurons where voltage-dependent calcium channels govern neurotransmitter release and synaptic plasticity. CACNA2D3 associates with multiple calcium channel isoforms encoded by genes including CACNA1A, CACNA1B, CACNA1C, and CACNA1D, but not T-type channels, indicating selective regulatory partnerships within the calcium channel superfamily.
CACNA2D3 is curated as a SFARI Category 2 gene (SFARI Cat 2), reflecting evidence implicating this locus in autism spectrum disorder risk. This classification suggests a probable role in ASD etiology, though the specific molecular mechanisms linking calcium channel dysregulation to autism phenotypes require further investigation.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.630
P2
not detected
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: -0.6304 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Genetic Evidence · ASD
Strong candidate — functional studies support ASD association
Source: SFARI Gene database · gene.sfari.org
This protein is implicated in both ASD and Alzheimer's Disease. View all cross-disease proteins →
Related Publications
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Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) but not T-type (CACNA1G) (By similarity)
Sources
Last updated 5/8/2026, 1:03:41 AM